Levetiracetam is indicated as adjunctive therapy in the treatment of partial onset seizures in adults with epilepsy. In clinical trials, daily doses of 1000 mg, 2000 mg and 3000 mg, given as twice-daily dosing, were shown to be effective. It is recommended that such treatments should be initiated with a daily dose of 1000 mg/day, given as twice-daily dosing (500 mg BID). Additional dosing increments may be given so as to reach a maximum recommended daily dose of 3000 mg. The currently commercially available tablets are available in strengths of 250 mg, 500 mg and 750 mg of levetiracetam making it very inconvenient for the patient to comply with the dosing regimen prescribed by the physician particularly when the patient may be stabilized at the higher daily dose.
Sustained or controlled release compositions have not been prepared and made available herebefore. In order to reduce dosing frequency, to improve patient compliance to dosing regimen, as well as to reduce peak related side effects there is a need to provide a controlled release composition of levetiracetam in a compact unit dosage form that is easily swallowable and releases levetiracetam in a controlled manner preferably at a uniform controlled rate. Controlling the rate of release of levetiracetam from a unit dosage form containing high amounts of about 500 mg to 1000 mg per tablet for twice daily dosing or containing 1000 mg to 1500 mg for once-daily dosing is a problem because of                (a) A very high solubility (104 g/100 ml) of levetiracetam which can not be decreased by altering the pH of the microenvironment and        (b) the requirement to have compact tablets that are easily swallowable precludes the use of known controlled release systems that use a large quantity of excipients including rate-controlling agents.        
The problem lies in not only slowing the rate of release of levetiracetam with a solubility as high as 104 g/100 ml from a compact dosage form but also providing a reproducible release at a controlled rate preferably uniform zero order rate while using very low amounts of rate-controlling agents.
WO00151033 ('033 application) discloses an oral solid pharmaceutical controlled release composition comprising excipients selected from inert, absorbent or lipidic matrices or mixtures thereof, an enterosoluble polymer and alkalizing agent. The alkalizing agent creates a microenvironment of higher pH in which the unionized less soluble pseudoephedrine is present in larger proportions and this contributes to the slower release. On the other hand the levetiracetam of the present invention is highly soluble in its unionized form itself, making the invention disclosed in '033 application unsuitable for the slow, controlled delivery of levetiracetam.